Abstract
Extracellular DNA (eDNA) is in the environment, bodily fluids, in the matrix of biofilms, and accumulates at infection sites. eDNA can function as a nutrient source, a universal biofilm matrix component, and an innate immune effector in eDNA traps. In biofilms, eDNA is required for attachment, aggregation, and stabilization of microcolonies. We have recently shown that eDNA can sequester divalent metal cations, which has interesting implications on antibiotic resistance. eDNA binds metal cations and thus activates the Mg2+-responsive PhoPQ and PmrAB two-component systems. In Pseudomonas aeruginosa and many other Gram-negative bacteria, the PhoPQ/PmrAB systems control various genes required for virulence and resisting killing by antimicrobial peptides (APs), including the pmr genes (PA3552–PA3559) that are responsible for the addition of aminoarabinose to lipid A. The PA4773–PA4775 genes are a second DNA-induced cluster and are required for the production of spermidine on the outer surface, which protects the outer membrane from AP treatment. Both modifications mask the negative surface charges and limit membrane damage by APs. DNA-enriched biofilms or planktonic cultures have increased antibiotic resistance phenotypes to APs and aminoglycosides. These dual antibiotic resistance and immune evasion strategies may be expressed in DNA-rich environments and contribute to long-term survival.
Highlights
SOURCE AND FUNCTIONS OF EXTRACELLULAR DNA Extracellular DNA is released from dead plant or microorganisms and accumulates in soil, aquatic, and sediment environments (Dell’Anno and Danovaro, 2005; Vlassov et al, 2007; Pietramellar et al, 2009)
The exception to the rule is in Caulobacter crescentus where Extracellular DNA (eDNA) blocks biofilm formation by binding to the polar holdfast structure, which is required for irreversible attachment (Berne et al, 2010). eDNA has been shown to localize to specific regions of mushroom-shaped microcolonies formed by P. aeruginosa in flow-chamber biofilms
FUTURE WORK To date, we have shown that eDNA influences the expression of several genes including a secreted DNase, and at least two operons controlled by the PhoPQ and PmrAB two-component systems
Summary
SOURCE AND FUNCTIONS OF EXTRACELLULAR DNA Extracellular DNA (eDNA) is released from dead plant or microorganisms and accumulates in soil, aquatic, and sediment environments (Dell’Anno and Danovaro, 2005; Vlassov et al, 2007; Pietramellar et al, 2009). DNA-INDUCED EXPRESSION OF THE pmr OPERON The pmr genes are required for the covalent addition of aminoarabinose to the 1- and 4 -phosphates of lipid A (Moskowitz and Ernst, 2010), which protects the outer membrane from AP treatment (Johnson et al, 2012), and is required for peptide resistance (Moskowitz et al, 2004; Lewenza et al, 2005).
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